A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus CAPOX Compared with Placebo Plus CAPOX as First-line Treatment of Subjects with Claudin (CLDN) 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
- Conditions
- Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) AdenocarcinomaMedDRA version: 20.0 Level: PT Classification code 10001150 Term: Adenocarcinoma gastric System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000519-26-HR
- Lead Sponsor
- Astellas Pharma Global Development, Inc. (APGD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 500
General Criteria:
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative (if applicable) prior to any study-related procedures.
2. Subject is considered an adult (e.g., = 18 years of age in the US) according to local regulation at
the time of signing the informed consent.
3. A female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at
screening; female subjects with elevated serum beta human chorionic gonadotropin (ßhCG) and a
demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3 Contraception Requirements] OR
- WOCBP who agrees to follow the contraceptive guidance as defined in [Appendix 12.3 Contraception Requirements] throughout the treatment period and for 6 months after the final study treatment administration.
4. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
5. Female subject must not donate ova starting at screening and throughout the study period, and for
6 months after the final study treatment administration.
6. A male subject with female partner(s) of childbearing potential:
- must agree to use contraception as detailed in [Appendix 12.3 Contraception Requirements] during the treatment period and for 6 months after the final study treatment administration.
7. A male subject must not donate sperm during the treatment period and for 6 months after the final
study treatment administration.
8. Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a
condom for the duration of the pregnancy or time partner is breastfeeding throughout the study
period and for 6 months after the final study treatment administration.
9. Subject agrees not to participate in another interventional study while receiving study drug in
present study.
Disease Specific Criteria:
10. Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
11. Subject has radiologically confirmed locally advanced unresectable or metastatic disease within
28 days prior to the first dose of study treatment.
12. Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of
study treatment. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
13. Subject’s tumor expresses CLDN18.2 in = 75% of tumor cells demonstrating moderate to strong
membranous staining as determined by central IHC testing.
14. Subject has a HER2-negative tumor as determined by local or central testing on a g
Prohibited Treatment or Therapies:
1. Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic
gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
2. Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ
adenocarcinoma unless the radiotherapy was completed > 28 days prior to the first dose of study
treatment. Subject who received palliative radiotherapy to peripheral bone metastases = 14 days
prior to first dose of study treatment and has recovered from all acute toxicities is eligible.
3. Subject has received treatment with herbal medications or other treatments that have known
antitumor activity within 28 days prior to first dose of study treatment.
4. Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subject using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) or a single dose of systemic corticosteroids is eligible.
5. Subject has received other investigational agents or devices within 28 days prior to first dose of
study treatment.
Medical History or Concurrent Disease:
6. Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
7. Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any
component of study treatment.
8. Subject has prior severe allergic reaction or intolerance to any component of CAPOX.
9. Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency. (NOTE: Screening for DPD deficiency should be conducted per local requirements.)
10. Subject has gastric outlet syndrome or persistent/recurrent vomiting.
11. Subject had recent gastric bleeding and/or is symptomatic with proven gastric ulcers that excludes
the subject from participation per investigator judgement.
12. Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection
or known active hepatitis B (positive HBs Ag) or C infection. For subjects who are negative for HBs Ag, but HBc Ab positive, an HB DNA test will be performed and if positive, the subject will be excluded. Subjects with positive serology but negative hepatitis C virus (HCV) RNA test results are eligible.
13. Subject has an active autoimmune disease that has required systemic treatment within the past
2 years.
14. Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to first dose of study treatment.
15. Subject has significant cardiovascular disease, including any of the following:
a) Congestive heart failure (defined as New York Heart Association [NYHA]
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method